University of Michigan, Ann Arbor, MI
Diabetes. 2020 Nov;69(11):2238-2245. doi: 10.2337/dbi19-0027.
While the field of islet biology has historically focused its attention on understanding β-cell function and the mechanisms by which these cells become dysfunctional with diabetes, there has been a scientific shift toward greater understanding of other endocrine cells of the islet and their paracrine role in regulating the β-cell. In recent years, many questions and new data have come forward regarding the paracrine role of the α-cell and specifically preproglucagon peptides in regulating insulin secretion. The role of intestinally secreted glucagon-like peptide 1 (GLP-1) in regulation of insulin secretion has been questioned, and a physiological role of pancreatic GLP-1 in regulation of insulin secretion has been proposed. In addition, in the last 2 years, a series of studies demonstrated a physiological role for glucagon, acting via the GLP-1 receptor, in paracrine regulation of insulin secretion. Altogether, this work challenges the textbook physiology of both GLP-1 and glucagon and presents a critical paradigm shift for the field. This article addresses these new findings surrounding α-cell preproglucagon products, with a particular focus on GLP-1, in the context of their roles in insulin secretion and consequently glucose metabolism.
虽然胰岛生物学领域的历史重点一直放在理解β细胞功能以及这些细胞在糖尿病中变得功能失调的机制上，但科学界已经发生了转变，更加关注胰岛的其他内分泌细胞及其旁分泌作用在调节β细胞中的作用。近年来，关于α细胞的旁分泌作用以及特定的前胰高血糖素肽在调节胰岛素分泌中的作用提出了许多问题和新的数据。肠分泌的胰高血糖素样肽 1 (GLP-1) 在调节胰岛素分泌中的作用受到质疑，并且提出了胰腺 GLP-1 在调节胰岛素分泌中的生理作用。此外，在过去的 2 年中，一系列研究表明，通过 GLP-1 受体发挥作用的胰高血糖素在胰岛素分泌的旁分泌调节中具有生理作用。总之，这项工作挑战了 GLP-1 和胰高血糖素的教科书生理学，并为该领域提出了一个关键的范式转变。本文针对围绕α细胞前胰高血糖素产物的这些新发现进行了探讨，特别关注 GLP-1 在胰岛素分泌及其随后的葡萄糖代谢中的作用。
